Method and apparatus for fractional flow reserve measurements

ABSTRACT

A method of determining fractional flow reserve (FFR) in a blood vessel having stenosis includes injecting fluid into the blood vessel upstream of the stenosis using a power fluid injector, measuring pressure drop across the stenosis, and calculating FFR from measured pressure drop. The injected fluid may comprise a contrast medium. Further actions may include placing a pressure sensor proximal of the stenosis, injecting fluid into the blood vessel upstream of the stenosis using the power fluid injector, and measuring pressure in the blood vessel proximal of the stenosis. The pressure sensor may then be repositioned to a position distal of the stenosis, fluid may be reinjected into the blood vessel upstream of the stenosis using the power fluid injector, and pressure may be measured in the blood vessel distal of the stenosis.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.13/534,864, filed Jun. 27, 2012, which claims the benefit of U.S.Provisional Application No. 61/501,472, filed Jun. 27, 2011, andentitled “Method and Apparatus for Fractional Flow ReserveMeasurements,” the disclosures of each of which are incorporated hereinby this reference.

BACKGROUND

Field

The present disclosure is directed to methods and apparatus fordetermining fractional flow reserve (FFR) which is a method ofidentifying the effect of an occlusion on blood flow in vasculature.Occlusions could result from a buildup of plaque, a thrombus, or anyother material that prevents normal or optimal blood flow.

Description of Related Art

Occlusions in vasculature can be the result of the buildup of plaque, athrombus, or any other material that prevents normal or optimal bloodflow. Vascular diseases are often manifested by reduced blood flow dueto atherosclerotic occlusion of vessels. For example, occlusion of thecoronary arteries supplying blood to the heart muscle is a major causeof heart disease. Numerous methods are currently available for treatingvarious lesion types, such as percutaneous transluminal angioplasty(PTCA), cutting balloon angioplasty, directional coronary atherectomy(DCA), rotational coronary atherectomy (RCA), ultrasonic breakingcatheter angioplasty, transluminal extraction catheter (TEC)atherectomy, rotablator atherectomy, and excimer laser angioplasty(ELCA). Often, stents are placed within the lesion so as to preventre-closure of the vessel (also known as recoil).

Lesion characteristics, together with vessel condition proximal anddistal to the lesion and vascular bed condition, are used to determinethe medically and economically optimal treatment method or combinationof methods of choice. Geometry, pressure, and flow are three variablesoften measured in the cardiovascular system. These measurements areperformed prior to, during, and after the treatment, providingdiagnostic and therapeutic data. The measurement prior to the treatmentallows careful treatment selection. Measurements during and after thetreatment enable evaluation of the treatment efficacy.

Lesion geometry is evaluated by angiography, qualitative coronaryangiography (QCA), or by intravascular ultrasound (IVUS). Thesemeasurements allow calculation of the percent diameter stenosis(angiography or QCA) or percent area stenosis (IVUS). This informationis used to estimate stenosis severity, but clinicians have realized thatdirect physical information about pressure and flow is necessary forcomplete evaluation of coronary artery disease. Physiologicalmeasurements such as pressure gradient have been clinically used as anindicator for lesion severity. However, previous attempts to relate thepressure gradient across the stenosis to its functional significancehave been disappointing without the use of a pharmacological agent, suchas a vasodilator, that artificially increases heart rate. The decreasein the pressure gradient after PTCA has been used to assess the successof the treatment, with poor correlation. Thus, the use of a vasodilatorto increase flow rate has been an important component of the foregoingmeasurement calculations.

Other parameters have been defined and proven more effective asindicators for lesion severity. The coronary flow velocity reserve(CFVR) is defined as the ratio of hyperemic to baseline flow velocity.The fractional flow reserve (FFR) is defined as the ratio of distal (tostenosis) pressure (Pd) to aortic pressure (Pa) during hyperemia.Hyperemic conditions are obtained by administration of vasodilators(e.g., papaverine, adenosine). Clinical studies have demonstrated that,in most cases, lesions with CFVR<2 must be treated using one of thepreviously mentioned methods, whereas for patients with CFVR>2,angioplasty may be avoided. Similarly, in many cases interventions, suchas angioplasty, may be avoided if FFR>0.75. Coronary flow occursessentially during diastole while systolic contribution to totalcoronary flow is smaller. A notable difference between diastolic tosystolic velocity ratio (DSVR) was observed between normal and stenoticarteries.

The FFR and CFVR are independent but complementary indicators. The firstcharacterize the specific lesion whereas the second is a more globalparameter, characterizing the lesioned vessel (lesion and distal bed).Clinical studies (Di Mario et al., Catherization and Cardiac Diagnosis38, 189-201, 1996) show that for approximately 75% of the patients, CFVRand FFR lead to the same conclusion regarding the lesion significance.At the same time, for 25% of the patients, the conclusions regardinglesion significance were different. This means that simultaneousdetermination of coronary flow reserve and fractional flow reserve isimportant and gives the clinician the additional and more completeinformation regarding the lesion severity.

Technical progress has been made recently with respect to pressure andvelocity monitoring guide wires. For example, 0.014″ PressureWire® (RadiMedical System, Uppsala, Sweden) is now available for intracoronarypressure measurements. Another maker of pressure wires is VolcanoCorporation and sold under the trade name FloWire®. Additionally, thesemeasurements may be performed using diagnostic low profile catheters,Millar pressure transducer catheters (available by Millar Instruments,Inc., Houston, Tex., U.S.A.), or any other intravascular pressureequipment.

A 0.014″ doppler flow wire (Cardiometrics Inc., Mountain View, Calif.)is also available for intracoronary velocity measurements. These wiresmay be advanced into distal parts of the coronary tree withoutsignificantly impeding the flow. Simultaneous measurements of FFR andCFVR require the use of both wires and/or a wire with multiple sensors.Such a procedure is complicated, expensive, and used only for researchpurposes. Therefore, clinicians use either velocity measurements tocalculate coronary flow velocity reserve (CFVR) or pressure measurementsto calculate fractional flow reserve (FFR). Furthermore, the flow wireis sensitive to the location of the tip within the vessel cross section.The wire tip will measure accurately if located along the longitudinalaxis. However, significant errors will appear once the wire is withinthe boundary layer. Therefore, manipulating the flow wire requires highexpertise and a lot of experience. Fortunately, these limitations arenot relevant to the pressure wire measurements, yielding accurate datawith simple handling.

Relevant United States patents and publications in the field of methodsand apparatus for determining fractional flow reserve (FFR) in bloodvessels include U.S. Pat. No. 6,089,103 to Smith; U.S. Pat. No.6,354,999 to Dgany et al.; U.S. Pat. No. 6,471,656 to Shalman et al.;U.S. Pat. No. 6,565,514 to Svanerudh et al.; U.S. Pat. No. 6,615,667 toSmith; U.S. Pat. No. 6,672,172 to Tulkki et al.; U.S. Pat. No. 6,754,608to Svanerudh et al.; U.S. Pat. No. 7,454,244 to Kassab et al.; U.S. Pat.No. 7,775,988 to Pijls, each incorporated herein by reference in theirentirety for this purpose. U.S. Patent Application Publication No.2009/0234231 to Knight et al. and International Publication No. WO2010/033971 to Kassab likewise are directed to known methods andapparatus for determining fractional flow reserve (FFR) in a bloodvessel and are incorporated herein by reference in their entirety forthis purpose.

SUMMARY

In one desirable embodiment, an Avanta™ power injector provided as partof an Avanta™ Fluid Management Injection System manufactured by Medrad®,Inc. comprises an FFR measurement mode or capability. This mode orcapability provides a clinician with the ability to achieve and identifya maximum flow rate for FFR measurement without using a vasodilator.Additionally, the FFR measurement mode or capability may instruct theclinician on how to operate the device to capture the greatest pressuredifference in the presence of a maximum flow rate. Thus, in a firstpressure measurement technique or procedure, supported by the Avanta™Fluid Management Injection System, an FFR software mode is provided andno disposable or hardware changes are required in the Avanta™ FluidManagement Injection System. The FFR modification only involves changesto the software control system. In a second measurement techniquediscussed in detail herein, simultaneous pressure measurements of anocclusion or stenosis are taken. This alternative system, technique, orprocedure allows for two sensing systems to quantify the effect of anocclusion on blood flow in a single measurement.

The various embodiments described in this disclosure may be used toidentify the presence of a stenosis with traditional angiography andthen quantify the lesion with saline or other harmless fluid. A dualsyringe power injector may also be used in the various embodiments ofthis disclosure, such as the dual syringe power injector disclosed inInternational Application No. PCT/US2010/042501 bearing InternationalPublication No. WO 2011/011346 A1, incorporated herein by reference inits entirety.

This disclosure also provides multiple embodiments for taking pressuremeasurements in a blood vessel. In one embodiment, a pressure sensingarrangement for acquiring simultaneous proximal and distal pressurereadings across the stenosis comprises a guide wire supporting opticalsensors and micro-electromechanical systems (MEMS) based sensors. Inanother embodiment, a pressure sensing arrangement for acquiringsimultaneous proximal and distal pressure readings across the stenosiscomprises implantable support rings for supporting pressure sensors andthe like, proximal and distal of the stenosis. In another embodiment, apressure sensing arrangement for acquiring simultaneous proximal anddistal pressure readings across the stenosis comprises an implantablestent for supporting pressure sensors and the like, proximal and distalof the stenosis. In a further embodiment, a pressure sensing arrangementfor acquiring simultaneous proximal and distal pressure readings acrossthe stenosis comprises an umbrella or inferior vena cava (IVC) filterfor supporting pressure sensors and the like, proximal and distal of astenosis.

Often an occlusion or stenosis occurs in a bifurcation in a bloodvessel, and a multi-pressure wire arrangement is described herein fordetermining pressure proximal and distal of the stenosis. Themulti-pressure wire arrangement may alternatively comprise one or moreoptical sensors, such as four (4) optical sensors or MEMs based sensors,for determining pressure proximal and distal of the stenosis. In anotherembodiment, multiple hemodynamic catheters or hemodynamic pressuretransducers may be used to determine pressure proximal and distal of astenosis at a bifurcation in a blood vessel. In a further embodiment, acombination of pressure wires and hemodynamic catheters may be used todetermine pressure proximal and distal of a stenosis at a bifurcation ina blood vessel. Additionally, a thrombus removal catheter comprisingpressure sensors may be used to determine pressure proximal and distalof a stenosis in a blood vessel.

One method of determining fractional flow reserve (FFR) in a bloodvessel having stenosis comprises injecting fluid into the blood vesselupstream of the stenosis using a power fluid injector, measuringpressure drop across the stenosis, and calculating FFR from measuredpressure drop. The injected fluid may comprise a contrast medium.

Additional parts of the method may comprise placing a pressure sensorproximal of the stenosis, injecting fluid into the blood vessel upstreamof the stenosis using the power fluid injector, and measuring pressurein the blood vessel proximal of the stenosis. Injecting fluid into theblood vessel may be reduced, limited, or discontinued when retrogradeflow is present in the blood vessel. Injecting fluid into the bloodvessel may be reduced, limited, or discontinued after a preset period oftime or after a pressure measurement has been taken.

Further parts of the method may comprise repositioning the pressuresensor to a position distal of the stenosis, reinjecting fluid into theblood vessel upstream of the stenosis using the power fluid injector,and measuring pressure in the blood vessel distal of the stenosis.Reinjecting fluid into the blood vessel may be reduced, limited, ordiscontinued when retrograde flow is present in the blood vessel.Reinjecting fluid into the blood vessel may be reduced, limited, ordiscontinued after a preset period of time or after a pressuremeasurement has been taken. Measuring pressure drop across the stenosismay comprise calculating the ratio of distal pressure to proximalpressure in the blood vessel. The FFR result may be displayed on a userinterface display associated with the power fluid injector.

In another embodiment, a method of determining fractional flow reserve(FFR) in a blood vessel having stenosis comprises inserting amulti-lumen catheter into the blood vessel, injecting fluid into theblood vessel upstream of the stenosis using a power fluid injector,measuring pressure drop across the stenosis, and calculating FFR fromthe measured pressure drop. The injected fluid may comprise a contrastmedium. The multi-lumen catheter may comprise at least a fluid injectingor conducting lumen and a hemodynamic monitoring lumen.

The method may further comprise placing a pressure sensor proximal ofthe stenosis, injecting fluid into the blood vessel upstream of thestenosis using the power fluid injector, and measuring pressure in theblood vessel proximal of the stenosis. Injecting fluid into the bloodvessel may be reduced, limited, or discontinued when retrograde flow ispresent in the blood vessel. Injecting fluid into the blood vessel maybe reduced, limited, or discontinued after a preset period of time orafter a pressure measurement has been taken. Measuring pressure in theblood vessel proximal of the stenosis may comprise substantiallysimultaneously measuring pressure using the pressure sensor and ahemodynamic monitoring port on the multi-lumen catheter. Additionalparts of the method may comprise repositioning the pressure sensor to aposition distal of the stenosis, reinjecting fluid into the blood vesselupstream of the stenosis using the power fluid injector, andsubstantially simultaneously measuring pressure in the blood vesseldistal of the stenosis using the pressure sensor and proximal of thestenosis via a hemodynamic monitoring port on the multi-lumen catheter.Reinjecting fluid into the blood vessel may be reduced, limited, ordiscontinued when retrograde flow is present in the blood vessel. Thestep of reinjecting fluid into the blood vessel may be reduced, limited,or discontinued after a preset period of time or after a pressuremeasurement has been taken.

Further parts of the method may comprise repositioning the pressuresensor to a position proximal of the stenosis, reinjecting fluid intothe blood vessel upstream of the stenosis using the power fluidinjector, and substantially simultaneously measuring pressure in theblood vessel proximal of the stenosis using the pressure sensor and thehemodynamic monitoring port on the multi-lumen catheter. Injecting fluidinto the blood vessel may be reduced, limited, or discontinued whenretrograde flow is present in the blood vessel. Injecting fluid into theblood vessel may be reduced, limited, or discontinued after a presetperiod of time or after a pressure measurement has been taken. Measuringpressure drop across the stenosis may comprise calculating the ratio ofdistal pressure to proximal pressure in the blood vessel. The FFR resultmay be displayed on a user interface display associated with the powerfluid injector.

Further details and advantages of the various embodiments described indetail herein will become clear upon reviewing the following detaileddescription of the various embodiments in conjunction with theaccompanying drawing figures, where like parts are designated by likereference numerals throughout.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graphical view showing waveform patterns of minimal tosevere stenosis in a blood vessel.

FIG. 2 is a view of a user interface display for a power injectorshowing an exemplary FFR menu.

FIG. 3 is a schematic view of a blood vessel with a stenosis.

FIG. 4 is a view of the user interface display for a power injectorshowing an FFR menu and a first step for determining FFR comprisingidentifying maximum flow rate in the blood vessel of FIG. 3.

FIG. 5 is a schematic view of the blood vessel with the stenosis of FIG.3 and showing a maximum flow rate in the blood vessel.

FIG. 6 is a view of the user interface display for a power injectorshowing an FFR menu and a second step for determining FFR comprisinginserting a pressure wire into the blood vessel of FIG. 3.

FIG. 7 is a schematic view of the blood vessel with the stenosis of FIG.3 and showing a pressure wire inserted into the blood vessel.

FIG. 8 is a view of the user interface display for a power injectorshowing an FFR menu and a third step for determining FFR comprisinginitiating maximum flow rate in the blood vessel of FIG. 3 and recordingpressure proximal of the stenosis.

FIG. 9 is a schematic view of the blood vessel with the stenosis of FIG.3 after initiating maximum flow rate in the blood vessel to recordpressure proximal of the stenosis.

FIG. 10 is a view of the user interface display for a power injectorshowing an FFR menu and a fourth step for determining FFR comprisingrepositioning the pressure wire in the blood vessel of FIG. 3.

FIG. 11 is a schematic view of the blood vessel with the stenosis ofFIG. 3 and showing the repositioned pressure wire in the blood vessel.

FIG. 12 is a view of the user interface display for a power injectorshowing an FFR menu and a fifth step for determining FFR comprisinginitiating maximum flow rate in the blood vessel of FIG. 3 and recordingpressure distal of the stenosis.

FIG. 13 is a schematic view of the blood vessel with the stenosis ofFIG. 3 after initiating maximum flow rate in the blood vessel to recordpressure distal of the stenosis.

FIG. 14 is a view of the user interface display for a power injectorshowing an FFR menu and a sixth step for determining FFR comprisingvalidating the FFR pressure reading.

FIG. 15 is a schematic view of the blood vessel with the stenosis ofFIG. 3 after initiating maximum flow rate in the blood vessel andsubsequent validation of the pressure readings.

FIG. 16 is a view of a user interface display for a power injectorshowing an alternative embodiment of an exemplary FFR menu.

FIG. 17 is a schematic view of a blood vessel with a steno sis.

FIG. 18 is a view of the user interface display for a power injectorshowing an FFR menu comprising identifying maximum flow rate in theblood vessel of FIG. 17.

FIG. 19 is a schematic view of the blood vessel with the stenosis ofFIG. 17 and showing a maximum flow rate in the blood vessel.

FIG. 20 is a view of the user interface display for a power injectorshowing an FFR menu comprising inserting a pressure wire into the bloodvessel of FIG. 17.

FIG. 21 is a schematic view of the blood vessel with the stenosis ofFIG. 17 and showing a pressure wire inserted into the blood vessel.

FIG. 22 is a view of the user interface display for a power injectorshowing an FFR menu comprising acquiring proximal and distal pressurereadings across the stenosis.

FIG. 23 is a schematic view of the blood vessel with the stenosis ofFIG. 17 to acquire the proximal and distal pressure readings across thestenosis.

FIG. 24 is a schematic view of the blood vessel with the stenosis ofFIG. 17 showing an alternative of a pressure sensing arrangement foracquiring simultaneous proximal and distal pressure readings across thestenosis.

FIG. 25 is a schematic view of the blood vessel with the stenosis ofFIG. 3 or FIG. 17 showing a guide wire supporting optical sensors.

FIG. 26 is a schematic cross-sectional view of the guide wire of FIG.25.

FIG. 27 is a schematic view of a fluid path set for use with a powerinjector to determine FFR in a blood vessel.

FIG. 28 is a schematic view of a blood vessel with a stenosis andshowing implantable support rings for supporting pressure sensors andthe like, proximal and distal of the stenosis.

FIG. 29 is a schematic view of a blood vessel with the stenosis of FIG.28 showing the implantable support rings proximal and distal of thestenosis and a stent disposed between the support rings.

FIG. 30 is a schematic view of a blood vessel with a stenosis andshowing an implantable stent for supporting pressure sensors and thelike, proximal and distal of the stenosis.

FIG. 31 is a schematic view of an umbrella filter for supportingpressure sensors and the like, proximal and distal of a stenosis.

FIG. 32 is a schematic view of a bifurcated blood vessel with a stenosisand showing a multi-pressure wire arrangement for determining pressureproximal and distal of the stenosis.

FIG. 33 is a schematic view of a bifurcated blood vessel with thestenosis of FIG. 32 and showing a multi-pressure wire arrangementcomprising four optical sensors for determining pressure proximal anddistal of the stenosis.

FIG. 34 is a schematic view of a bifurcated blood vessel with thestenosis of FIG. 32 and showing use of three hemodynamic catheters fordetermining pressure proximal and distal of the stenosis as analternative to the pressure sensing arrangements shown in FIGS. 32-33.

FIG. 35 is a schematic view of a bifurcated blood vessel with a stenosisof FIG. 32 and showing use of a combination of pressure wires andhemodynamic catheters for determining pressure proximal and distal ofthe stenosis as an alternative to the pressure sensing arrangementsshown in FIGS. 32-34.

FIG. 36 is a schematic view of a blood vessel with a stenosis showing athrombus removal catheter comprising pressure sensors for determiningpressure proximal and distal of the stenosis as an alternative to thepressure sensing arrangements shown in FIGS. 32-35.

FIG. 37 is a schematic view of a fluid delivery system operable todeliver fluid flow in an optimized manner.

FIG. 38 is a graph of Reynolds Number vs. Artery Diameter Reduction usedto describe aspects of the methods of determining FFR described herein.

FIG. 39 is a graph of Theoretical FFR Value with Blood and ContrastTransform Function used to describe aspects of the methods ofdetermining FFR described herein.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

For purposes of the description hereinafter, spatial orientation terms,as used, shall relate to the referenced embodiment as it is oriented inthe accompanying drawing figures or otherwise described in the followingdetailed description. However, it is to be understood that theembodiments described hereinafter may assume many alternative variationsand configurations. It is also to be understood that the specificcomponents, devices, features, and operational sequences illustrated inthe accompanying drawing figures and described herein are simplyexemplary and should not be considered as limiting.

In this disclosure, various embodiments of a method and system areprovided that use a power injector to push fluid through a blood vesselwhile making an FFR measurement. Conventional FFR practice involvesadministering a pharmaceutical known as a vasodilator to a patient. Thisdrug increases blood flow across a measured area by pacing the heart toincrease cardiac output. Based on this increase, the pressuredifferential is measured through increases using one or a plurality ofsensors. Instead of increasing the pacing of the heart, injecting fluidat a controlled rate using a power injection normalizes pressures to amaximal amount that a particular vessel can support as identifiedthrough retrograde flow R in the Figures. The use of a power injectoralso provides the capability to ensure protocol-based or maximizedpressure differential across a lesion.

In cases where differential viscosity fluids are used with lesser flowrates, the viscosity differences produce an image with standard pressurewaveforms similar to hemodynamic signals. Such waveforms are familiar toclinicians who routinely observe pressure waveforms on a hemodynamicmonitor during cardiac procedures. Typical waveform patterns showingminimal to severe stenosis are shown in FIG. 1. Pressure differences arestill be magnified at the lesion site due to the increased bloodviscosity differences alone. Various fluid mechanics formulas may beused to determine pressure drop in a conduit, such as a blood vessel.One such equation is Darcy-Weishbach: ΔP=f×L/D×((ρ×V×D)/2); where:ΔP=pressure drop; f=friction factor; L=artery restriction length;D=average diameter of restricted artery; ρ=density of fluid; V=velocityof fluid. Another such equation is: Q=A×V; where: Q=flow rate;A=cross-sectional area of restriction; V=velocity of fluid. A thirdequation for use in determining pressure drop in a conduit is: f=64/Re;where: f=friction factor and Re=Reynolds number. A fourth equation foruse in determining pressure drop in a conduit is: Re=(ρ×V×D)/μ; where:Re=Reynolds number; ρ=fluid density; V=velocity of fluid; D=diameter ofrestriction artery; and μ=fluid viscosity.

Accordingly, to increase the measured pressure drop during FFR withoutusing pharmaceuticals, the following discussed relationships may bedetermined. First, the measured pressure drop across the blood vesselrestriction increases as the flow rate increases across the restriction.As noted previously, current practice is to use a vasodilatorpharmaceutical to increase blood flow rate. The present method increasesflow across the restriction using a steady state and controlledinjection fluid across the restriction administered by a power injector,thus causing an increased pressure drop or differential without the needfor a pharmaceutical. Next, the pressure differential increases acrossthe restriction as the viscosity of the injected fluid across therestriction increases. In current practice, known FFR measurementtechniques typically use the patient's blood. In the present method, thepower injector may use a more viscous media such as contrast. Third, theuse of a power injector enables the measured pressure drop across arestricted artery to be more accurately correlated to a percentagerestriction of the blood vessel (e.g., an artery) without usingpharmaceuticals. A suitable power injector for the foregoing applicationincludes an Avanta™ Fluid Management Injection System manufactured byMedrad®, Inc., and disclosed in U.S. Pat. Nos. 7,549,977 and 7,563,249,incorporated herein by reference for details relating to power injectorssuitable for the present method.

In one embodiment, an FFR measurement feature may be integrated with anAvanta™ Fluid Management Injection System. In this embodiment, two (2)measurement techniques may be supported with the Avanta™ power injector.This pressure measurement technique involves incorporating an FFRsoftware mode in the Avanta™ Fluid Management Injection System. In thismeasurement technique, no physical changes to the disposable andhardware portions of the Avanta™ Fluid Management Injection System arerequired, and the only changes needed are software modifications to thesoftware control system. A second measurement technique involvessimultaneous pressure measurements of an occlusion in a blood vessel.This technique allows for two sensing elements to quantify the effect ofan occlusion on blood flow in a single measurement.

Referring to FIGS. 2-15, an FFR measurement system 10 is depictedsituated in a blood vessel V, such as an artery. This system 10 uses thecurrent physical platform of an Avanta™ power fluid injector 2 withmodifications to the software control system of the control unit 4 ofthe power fluid injector 2, as noted above, which provide a mechanism toinject viscous fluid across an occlusion, lesion, or stenosis S at highflow rates. FFR measuring devices are then be able to quantify stenosispresence S and effect without pacing the heart through a pharmaceuticalvasodilator. In FIG. 2, an exemplary Avanta™ user interface screen 12(e.g., graphical user interface (GUI)) displays the FFR mode, and theuser is guided through a series of steps. The user interface screen 12provides instructions and indicators on how to complete the FFRmeasurement. Referring to FIGS. 4-5, an initial step in the FFRmeasurement process is depicted. In this step, the clinician, such as aphysician, identifies the maximum contrast flow for the FFR measurementby injecting contrast medium C via a catheter 14 connected to theAvanta™ power fluid injector 2. Initially, the clinician positions thecatheter 14 where contrast can be injected under pressure into thedirection of blood flow B. The clinician then initiates the contrastinjection with a variable hand controller (not shown) associated withthe Avanta™ Fluid Management Injection System through the catheter 14.Once retrograde flow R is observed, the maximum flow rate has beenachieved. The clinician “saves” this flow rate by pressing, for example,a side (saline) button on the hand controller or by another input to theAvanta™ control system, such as by pressing a button on the userinterface screen 12. U.S. Pat. No. 7,313,431 to Uber et al. discloses amethodology for determining retrograde flow R in a blood vessel V, andthis patent is incorporated herein by reference for this purpose.

The next step in the FFR measurement process is depicted in FIGS. 6-7.In this step, the clinician places a pressure wire 20 supporting apressure sensor 22 prior to the beginning of the stenosis S. This wire20 is introduced using established clinical technique in the same manneras a traditional guide wire. It is desirable to give consideration toensuring that the contrast medium C does not “jet” across the stenosisS, and side-hole catheters are desirable for this application such as aVanguard Dx® Angiographic Catheter manufactured by Medrad®, Inc. anddisclosed in U.S. Patent Publication No. US 2007/0073271 to Brucker etal., incorporated herein by reference.

Next, the method comprises acquiring a first pressure reading, asdepicted by FIGS. 8-9. In this step, the system 10 acquires the firstpressure reading via pressure sensor 22 through the support of theAvanta™ power fluid injector 2, and contrast flow C is initiated withthe use of the hand controller. In this step of the method, the handcontroller acts as a trigger to start a fluid injection in the directionof blood flow B. Once started, the fluid injection continues for threeseconds (or other programmed time) at the maximum flow rate determinedin the first method step discussed previously. As the fluid injectioncommences, flow rate and pressure increase in the blood vessel V. Thispressure is measured by the pressure sensor 22 (e.g., a pressuretransducer) on the pressure wire 20 and is retrieved by the controlsystem of the Avanta™ Fluid Management Injection System. Conditioninglogic or other signal filtering techniques in the control system of theAvanta™ Fluid Management Injection System can be employed to prevent afalse reading by comparing the output of the pressure sensor 22 before,during, and after the fluid injection. Additionally, sensed conditionsare verified to ensure that the pressure sensor 22 does not becomelodged into the wall of the blood vessel V. Previous steady statemeasurements may be employed to ensure the “reasonability” of thereturned pressure measurements. Feedback could signal termination of thefluid injection through an Imaging System Interface (ISI) port if thereturned signals are not as anticipated. After the fluid injection,pressure normalizes in the blood vessel V and the beginning and endingpressure become the same. Pressure measured during the fluid injectionmay be filtered for transients along with fluid rise and fallconditions. The proximal pressure measurement is then stored in theAvanta™ control system (e.g., control unit 4) for use in the FFRcalculation. While the various FFR measurement techniques described inthis disclosure suggest using an existing Avanta™ control system as asuitable control system or device, this should not be deemed exclusiveand any logical storage and computation device may also be used for FFRcalculations in the various embodiments in this disclosure.

In a further step in the FFR measurement process, the pressure wire 20is repositioned in the blood vessel V, as shown in FIGS. 10-11. In thisstep, the pressure wire 20 is moved distally past the stenosis S to aregion behind the occlusion to complete the pressure measurement. Thecatheter 14 remains in place for the duration of the measurement.Referring further to FIGS. 12-13, the second or distal pressuremeasurement may now be taken using the pressure sensor 22 on thepressure wire 20. The placement of the pressure sensor 22 past thestenosis S enables the pressure sensor 22 to be exposed to increasedflow rates and fluid pressure during a fluid injection. In this case,the hand controller acts as a triggering mechanism to commence theinjection of fluid, contrast media C, in the direction of blood flow B.The fluid is injected for three seconds (or other programmed time) whilethe second measurement is made. During the fluid injection, flow rateand pressure increase in the blood vessel V. This pressure increase ismeasured by the pressure sensor 22 and is retrieved by the controlsystem of the Avanta™ Fluid Management Injection System. Conditioninglogic through signal filtering may be employed to prevent a falsereading by comparing the output of the pressure sensor 22 before,during, and after the fluid injection. Additionally, sensed conditionsare verified to ensure the pressure sensor 22 does not become lodgedinto the wall of the blood vessel V. Previous steady state measurementsmay be used to ensure the “reasonability” of the returned pressuremeasurements. After the fluid injection, pressure normalizes in theblood vessel V, and the beginning and ending pressure become the same.The pressure measured during the fluid injection is filtered fortransients along with fluid rise and fall conditions. The second ordistal pressure reading is then stored in the control system of theAvanta™ Fluid Management Injection System for a later calculation. Theforegoing fluid injections in the blood vessel V may be accomplished viainjection of a contrast medium which may be diluted as desired bysaline, as described in U.S. Patent Application Publication No.2010/0114040 to Schriver et al., which discloses a mixing handcontroller of the Avanta™ Fluid Management Injection System.

FIGS. 14-15 show the validation or confirmation of the FFR measurement.As FIGS. 14-15 reveal, the FFR measurement can be validated in oneevent. As shown in FIGS. 14-15, the pressure sensor 22 starts at thedistal end of the stenosis, or a first (1^(st)) position of the pressuresensor 22 shown in FIG. 15. The hand controller acts as an injectiontrigger for a third and final time. The fluid injection is initiated andthe control system of the Avanta™ Fluid Management Injection Systemindicates that the first measurement is being taken through an audibleor visual indication or a combination thereof. After an additional twoseconds (or other programmed time), the Avanta™ power fluid injector 2alerts the clinician by indicating to the clinician to pull back on thepressure wire 20. The clinician pulls back to a location that isproximal to the stenosis S, or to a second (2^(nd)) position of thepressure sensor 22 shown in FIG. 15. Throughout this process, pressuremeasurements are taken using the pressure sensor 22. It can beanticipated that the maximum pressure is proximal to the stenosis S andthe minimum pressure is distal to the stenosis S. Time duration of thevalidation process can vary. Additionally, these pressure measurementscould also end with another initiation of the hand controller. FFR isthen calculated by Pd/Pp, and both the distal and proximal pressuremeasurements are filtered MAP (Mean Arterial Pressure) for effect. TheFFR value is calculated as a part of the foregoing describedmethodologies are the same, and differing values could indicateinaccurate technique. Both values are displayed to the clinician forreporting purposes. A quality metric may also provide the clinician withan indication that their measurements are consistent. The FFR values maybe stored and recalled as required. In some instances when interventionis required, the first set of FFR values may be compared with a secondset after the intervention. This comparison provides a before and afterlook at flow rate.

In a variation of the foregoing method, simultaneous pressuremeasurements may be taken, as illustrated in FIGS. 16-23. Thesimultaneous pressure measurement embodiment of the FFR measurementsystem 10 a is depicted in FIGS. 16-23. This system 10 a also usesAvanta™ Fluid Management Injection System with appropriate modificationto the control system and disposable set, and a power fluid injector 2 aand control unit 4 a therefor is shown schematically in these figures. Amodified multi-lumen catheter 40 comprising a first fluidconducting/injecting port or lumen 42 and a second hemodynamicmonitoring port or lumen 44 may be used in the system 10 a, andconnected to the power fluid injector 2 a. As with the foregoingembodiment of the FFR measurement system 10, the Avanta™ FluidManagement Injection System includes an FFR mode. The FFR mode may bevisually distinguishable from the normal operating mode based onbordering and other coloring effects on the user interface display 12 a,and provides the clinician with the ability to achieve and identify amaximum flow rate for FFR measurement. Additionally, the FFR modeinstructs the clinician on how to operate the device to capture thegreatest pressure difference in the presence of maximum flow rate.

In FIG. 16, an exemplary user interface display 12 a for the Avanta™Fluid Management Injection System is shown displaying the FFR mode. InFIG. 17, the blood vessel V is shown with a stenosis S in a similarmanner to FIG. 3. The user interface display 12 a is used to guide theuser through a series of operational steps, and the user interfacedisplay 12 a provides instructions and indicators on how to complete therequired measurements. Referring to FIGS. 18-19, the clinician firstidentifies the maximum contrast flow for the FFR measurement. In thismethod step, the clinician positions the catheter 40 to a position wherethe catheter 40 can inject contrast medium C under pressure via thefluid injecting lumen 42 using the power fluid injector 2 a. Theclinician then initiates the contrast medium C injection with thevariable hand controller from the Avanta™ Fluid Management InjectionSystem. Once retrograde flow R is observed, the maximum flow rate hasbeen achieved and the clinician “saves” this flow rate by pressing onthe side (saline) button on the hand controller or by another input tothe control system such as by pressing a button on the user interfacedisplay 12 a.

Referring next to FIGS. 20-21, the next FFR measurement method step isillustrated. In FIGS. 20-21, the clinician places the pressure wire 20 ajust prior to the beginning of the stenosis S. The pressure wire 20 asupporting one or more pressure sensors 22 a may be introduced usingestablished clinical technique in the same manner as a traditional guidewire. Again, consideration can be given to ensuring that the contrastmedium C does not “jet” across the across the stenosis S, and side-holecatheters are desirable for this application, as indicated previously.Ideally, the hemodynamic monitoring port or lumen 44 aligns with thepressure wire 20 a, so that both a hemodynamic monitoring port or lumen44 and the pressure sensor 22 a read the same hemodynamic signal.

FIGS. 22-23 next depict the acquisition of the first pressuremeasurement reading. In this step, the FFR measurement system 10 a isshown to acquire the first pressure reading through the support of theAvanta™ power fluid injector 2 a. Contrast medium C flow is initiatedwith the use of the hand controller from the Avanta™ Fluid ManagementInjection System, which actuates the power fluid injector 2 a to injectcontrast medium C. In this step of the process, the hand controller actsas a trigger to start a fluid injection using the Avanta™ power fluidinjector 2 a and contrast medium C in injected via the fluid injectingport or lumen 42 of the catheter 40. Once started, the fluid injectioncontinues for ten seconds (or other programmed amount) at the maximumflow rate determined previously. Pressure readings proximal or distal ofthe stenosis S are taken substantially simultaneously using the pressuresensor 22 a and the hemodynamic monitoring port or lumen 44 on thecatheter 40.

The Avanta™ control system typically initiates an audible and/or visualalert indicating to the user to start acquiring an FFR signal. Flow rateand pressure increase in the blood vessel V as fluid is injected by theAvanta™ power fluid injector 2 a and contrast medium C in injected viathe fluid injecting port or lumen 42 of the catheter 40. The fluidpressure is measured by the hemodynamic monitoring port or lumen 44 ofthe catheter 40 and by the pressure sensor 22 a at the first (1^(st))position shown in FIG. 23. Both readings are recorded by the Avanta™control system. Once the clinician is alerted, the pressure wire 20 a isadvanced past the stenosis S to the distal end thereof, where thepressure sensor 22 a is placed at a second (2^(nd)) position as shown inFIG. 23. Fluid, such as contrast medium C, is again injected into theblood vessel V using the power fluid injector 2 a via the fluidinjecting port or lumen 42 of the catheter 40 for a preset period oftime, such as 3 seconds, and until retrograde flow R is again observedin the blood vessel V. Pressure readings may be taken substantiallysimultaneously distal of the stenosis S using the pressure sensor 22 aand proximal of the stenosis S using the hemodynamic monitoring port orlumen 44 on the catheter 40.

Next, the clinician retracts the pressure wire 20 a to its startinglocation, where the pressure sensor 22 a is placed at a third (3^(rd))position as shown in FIG. 23, and fluid, such as contrast medium C, isagain injected into the blood vessel V using the power fluid injector 2a via the fluid injecting port or lumen 42 of the catheter 40 for apreset period of time, such as 3 seconds, and until retrograde flow R isagain observed in the blood vessel V. This last position is in thevicinity of the hemodynamic monitoring port or lumen 44 of the catheter40 and pressure readings may again be taken simultaneously using thepressure sensor 22 a and the hemodynamic monitoring port or lumen 44 ofthe catheter 40. Physicians/clinicians often use this last step tovalidate that the pressure readings before the stenosis S are readidentically by both sensors. If for any reason the pressure readings aredifferent, the physician or clinician may recalibrate and measure again.

Conditioning logic through signal filtering embedded as part of theAvanta™ control system prevents a false reading by comparing the outputof the pressure transducer 22 a before, during, and after the fluidinjection. Additionally, sensed conditions are verified to ensure thatthe pressure transducer 22 a does not become lodged into the wall of theblood vessel V. Previous steady state measurements may be used ensurethe “reasonability” of the returned pressure measurements. After thefluid injection, pressure normalizes in the blood vessel V and thebeginning and ending pressure become the same. Pressure measured duringthe fluid injection may be filtered for transients along with fluid riseand fall conditions. The pressure is then stored for use in the FFRcalculation. FFR is then calculated by Pd/Pp and both the distal andproximal pressures may be filtered for effect. FFR values may be storedand recalled as required. In instances when intervention is required,the first set of FFR values may be compared with a second set. Thisprovides a before and after look at flow rate as provided by FFRmeasurement.

A variation of the foregoing simultaneous measurement methodology isillustrated in FIG. 24. In this alternate method of simultaneouspressure measurement, a catheter 50 may be provided having a distal end52 defining a distal end opening 54 that allows for a dual pressuresensing wire 56 to extend past the distal end opening 54. The dualpressure sensing wire 56 comprises two pressure sensors 58(1), 58(2)axially spaced apart on the dual pressure sensing wire 56 so as toextend past the distal end opening 54. In this embodiment, side holes(not shown) on the catheter 50 diffuse fluid medium, contrast medium,while the distal end 52 allows for exact placement of the dual sensingpressure wire 56. This embodiment of the catheter 50 eliminates the needfor the clinician to reposition the catheter 50 once it is placed andonly the dual pressure sensing wire 56 needs positioning. The Avanta™power fluid injector 2 and control system or unit 4 may be used in theembodiment shown in FIG. 24.

In another embodiment, as shown in FIGS. 25-26, a guide wire 60 maycomprise numerous sensors 62. The guide wire 60 may define an internalcavity and have an optical shielding covering that protect againstX-rays. Certain known guide wires and/or catheters currently provide adamped way to view hemodynamic signals. However, these known devices canalso act as a medium for carrying optical wires used for transmittingpressure data. These known guide wires have internal cavities initiallydesigned to act in many of the same ways as a traditional catheter.Depending on the internal diameter (ID) of a guide wire, numerousoptical wires can be placed. In the guide wire 60 shown in FIG. 25, ametal based covering, such as Nitenol, may be used to enhance protectionfor internal optical wires 64 to guard against light and/or X-Rayemissions. Holes or cutouts may also be provided to enable the opticalsensors 62 to protrude from the guide wire 60 and/or a catheter. Thisfeature enables the external facing portion of the sensor 62 to exit theguide wire 60 and/or catheter while the internal portions remainprotected. Thus, only the sensing portions of the sensors 62 interactwith the pressure produced by blood flow in blood vessel V. Fluoroscopicmarkers may also be placed on the guide wire 60 and/or catheter tofacilitate placing a portion of the guide wire 60 proximal to thestenosis S and to ensure that an optical sensor 62 is placed distal ofthe stenosis S. This placement enables the measurement of the lesionwithout continual retries or sensor repositioning. The optical wires 64provide additional material in the guide wire 60 and/or catheter topermit greater torque to be applied to the guide wire 60 and/or catheterwhen placing the assembly in the blood vessel V. The guide wire 60 withoptical sensors 62 may be used with traditional FFR measurementtechniques such as increasing cardiac output through a vasodilator, andmay also be used in any of the FFR measurement techniques described inthe foregoing.

Referring next to FIG. 27, an FFR measuring catheter 70 for suitableapplication in connection with the Avanta™ Fluid Management InjectionSystem is disclosed in U.S. Pat. Nos. 7,549,977 and 7,563,249,incorporated herein by reference previously.

In a further embodiment, a carrier 100 may be provided to supportmultiple optical sensors and is shown in FIGS. 28-31. The carrier 100may include a variety of intra-arterial and venous devices or fluid thatenter the vasculature and help to identify and/or treat disease. Byadding pressure sensing capability to these devices, longer termmeasurement of performance characteristics through pressure dropmeasurements may be accomplished. The carrier 100 may be in the form of,for example: permanent and semi-permanent stents; umbrella filters;temporary implantable support rings for sensors, catheters of varioussizes, magnetically and other steerable devices, and fluid sail devices,as a set of non-limiting examples.

In FIG. 28, a carrier 100 in the form of an implantable support ringcarrier 102 is shown. The support ring carrier 102 is used to supportpressure sensors 104 on a bioabsorbable magnesium material or similarmaterial that will degrade over time. As identified in medicalliterature (see The Lancet, Volume 369, Issue 9576, incorporated here inby reference), this kind of material may be used to provideinfrastructure scaffolding to support the pressure sensors 104. In thepresent application, the pressure sensors 104 could be mounted on thedegradable material and then placed in regions where FFR measurement aidin the detection and quantification of stenosis S. The pressure sensors104 may also remain in such positions until any interventionalprocedures are complete.

In FIG. 29, the carrier 100, as illustrated in the embodiment shown inFIG. 28, is combined with a stent 110. Using this arrangement, aclinician may leave the measurement capability in place for a variety oftime frames that are dependent on prescribed treatment options. Forexample, the carrier 100 may be left for a period of minutes until thestent 110 is placed. Dilution solutions enable the supportingbioabsorbable material to degrade and the pressure sensors may beremoved 104. Additionally, the pressure sensors 104 may be left in thepatient for an extended period of time in order to monitor the effectsof thrombus on a particular region of interest. For example 30, 60, 90days of monitoring can provide enhanced knowledge of stent restenosis.This long term placement is especially useful in patients who do nothave conforming anatomy and are susceptible to restenosis. The carrier100 in FIG. 29 may be provided with pressure sensors 104 that may beused as part of a method of monitoring intra-arterial blood pressure inpatients over an extended period of time. One or more of the pressuresensors 104 enable constant monitoring of patients with chronicconditions. For example, patients with peripheral thrombus might havesensors mounted distally in the arms or legs and the signal supplied bythese pressure sensors 104 may be compared with a signal supplied byanother sensor located in the left ventricle. Collectively, thesepressure sensors 104 enable a clinician to compare the effects ofthrombus over time. Other pertinent applications for the carrier 100shown in FIG. 29 areas include early stroke warning and vital organmonitoring, as non-limiting examples.

In FIG. 30, the carrier 100 comprises a permanent or semi-permanentstent 120. In a similar manner to the embodiment of the carrier 100shown in FIG. 29, the stent carrier 120 may comprise pressure sensors124 that are placed on the deployed stent body. The pressure sensors 124may be used to provide a real-time knowledge of thrombus and otherocclusions. Output or signal lines (not shown) from the pressure sensors124 may be connected to a transmit-and-receive box located remotely fromthe stent carrier 120. This box may be configured to be primarilyresponsible for communicating the effects of blood flow on the stentcarrier 120. As the stent carrier 120 becomes occluded over time, aclinician would be able to measure its effective flow capacity.

In addition to the foregoing “ring” carrier 102 (FIG. 29) and stentcarrier 120 (FIG. 30), other applications for the stent carrier 100 mayinclude a battery powered device, similar to pacemakers. Additionally,microwave power can provide enough current to sample the pressuresensors 104, 124 and provide readings. Further, vibration technologycould also power such a device. In any of these embodiments, follow-upoffice type appointments enable caretakers to understand the performanceof, for example, the stent carrier 120.

Blood flow may or may not be altered during the pressure reading processin the various embodiment of this disclosure. Little or no increase toblood flow is not an ideal measurement, but does provide a mechanism toquantify performance based on relatively normal flow. However, sinceexercise increases blood flow and enhances accuracy, sampling during aphysical activity provides a desirable measurement situation. Pressurereadings can occur immediately after installation in the patient's bodyor over long periods of time. Depending on battery life or externalpower, pressure readings are available for the life of the stent carrier120. Any location in the body can provide an opportunity for pressuremeasurement, and the foregoing “ring” carrier 102 (FIG. 29) and stentcarrier 120 (FIG. 30) aid in the internal/external reading of suchpressures.

In FIG. 31, the carrier 100 comprises an umbrella filter carrier 130.Umbrella filters are commonly deployed in the inferior vena cava toprevent strokes like pulmonary embolisms. These devices are oftentemporary and removed when a patient is no longer at risk for bloodclots. Although primarily implemented in the inferior vena cava, anumbrella filter may also be placed in the infra-renal, supra-renal,supra-hepatic, and superior vena cava, among other locations. Multiplepressure sensors 134 can be placed on the umbrella filter carrier 130 todetect blood clots and other occlusions.

Often, coronary occlusions are found at the intersection points of acoronary tree. These intersection points might involve two, three, ormore pathways. With reference now to FIGS. 32-35, in another embodiment,multiple pressure wires 200 may be placed down a bifurcation 202 in ablood vessel V having a stenosis S, and each vessel branch 204 receivesone or more pressure and/or flow measuring sensors 214. Collectively,the pressure and/or flow measured from these sensors 214 total thecardiac output from the “root” or supplying branch 204. In the caseswhere a stenosis S is found, the combined pressure drop is indicative ofan occlusion. In the present embodiment, three (3) separate occlusionsor stenoses S are illustrated in FIGS. 32-35, and each of theseocclusions or stenoses S is located in the vicinity of the intersectionpoint or bifurcation 202. These illustrations are exemplary and areintended to depict one, two, three, or more locations where occlusionsoccur at or around the bifurcation 202. Similar conditions also exist atblood vessel trifurcations. In the pressure sensing arrangement shown inFIG. 32, three (3) pressure sensors 214 are deployed. In the pressuresensing arrangement shown in FIG. 33, four (4) pressure sensors 214 aredeployed. In the pressure sensing arrangement shown in FIG. 34, three(3) hemodynamic monitoring catheters 224 are deployed. In the pressuresensing arrangement shown in FIG. 35, two (2) pressure sensors 214 aredeployed in one vessel branch 204 and a hemodynamic monitoring catheter224 is deployed in the second vessel branch 204.

In another embodiment, FFR measurement capability may be provided on athrombus removal catheter, as shown in FIG. 36, for the purposes ofproviding feedback to the clinician about the performance of aspirationactivity, reducing contrast load and hemolysis, etc. For example, anymanual catheters, assisted manual catheters, and mechanical thrombusremoval catheters may be used in the embodiment shown in FIG. 36.

In the embodiment shown in FIG. 36, a thrombus removal catheter 300 isshown with several small pressure sensors 314, similar to common fiberoptic or miniature MEMs based physiological pressure sensors, arelocated along the length of a thrombus removal catheter 300. Thepressure sensors 314 are typically flush with the exterior wall of thecatheter 300. Specifically, two (2) pressure sensors 314 may be locatednear a distal end 302 of the catheter 300 in the vicinity of theaspiration point or tip 304. The two (2) distal pressure sensors 314 maybe separated by a distance that is most appropriate for the size oflesion or thrombus that is common to a particular region. Additionalpressure sensors (not shown), such as a third or fourth sensor, may belocated several inches from the aspiration opening or tip 304, and theseadditional sensors can provide details about lengthy thrombus bloodclots that have gradual effects on blood flow. Signal wires (not shown)may be embedded through the length of the catheter 300. The catheter 300may have additional connection points at the proximal end, which can beused to convert optical or MEMs signals to electrical pressure waves.Pressure waves and FFR calculations may then be displayed on the Avanta™user interface display or other console. Electrical signals may also beprovided to other hemodynamic monitoring systems for additionalmonitoring and display.

In one exemplary application of the thrombus removal catheter 300 shownin FIG. 36, a clinical “use case” using the catheter 300 may include thesteps of: (1) diagnosing a thrombus during an angiogram with supportfrom a power injector; (2) retrieving a diagnostic catheter (ifrequired); (3) inserting the thrombus removal catheter 300 into thepatient's blood vessel V having the thrombus; (4) measuring the initialthrombus occlusion effect on blood flow; (5) beginning aspiration of theaffected area using the thrombus removal catheter 300; (6) pausingaspiration; (7) measuring the remaining effect of thrombus occlusion onblood flow; (8) determining if enough thrombus has been removed; andrepeating forgoing steps (5)-(8) as needed.

The various embodiments of the FFR measurement system and method in thisdisclosure are advantageous because a power injector is used to pushfluid through a blood vessel so that adenosine and other pharmaceuticalsdo not have to be administered during FFR procedures. Thus, a personsuspected of having heart disease does not have to receive a drug thatpaces the heart to the maximum possible cardiac output. Moreover, flowrate is controlled externally and the heart remains unaffected.Protocol-based fluid delivery also increases the flow rate to a plateaulevel each and every time, enabling maximum pressure differential andthis ensures a more “correct” objective number of flow diminishment.Further, the process is an “on demand” feature because the powerinjector is constantly available and measurements may be taken andrepeated at any time. Objective evidence is gained over time and theprocess may be repeated numerous times as needed.

The foregoing embodiments of the FFR measurement system and methodenable Interventional Radiology (IR) clinicians to have maximum flowacross a suspect region. Normally, IR clinicians would not use avesolator dilator. In most cases, IR clinicians would refer the patientto Interventional Cardiologists (IC) clinicians, and the embodiments ofthe FFR measurement system and method opens FFR opportunities to IRclinicians.

Additionally, nitroglycerine and other vasodilators can still beprescribed without interference to the FFR test, and patients takingphosphodiesterase inhibitors like Viagra® do not need to come off of thedrug for the testing. Further, after an initial characterization ofideal fluid flow with one medium, like contrast, additional fluid flowscould be substituted with similar effect. The various embodimentsdescribed in this disclosure are further applicable to heart valve orother structural diseases. Patients with these afflictions may not beable to circulate blood at maximum hyperemia and may not benefit fromcurrent FFR techniques. Accordingly, giving the patient a vasodilatorincreases the pacing of the heart, but does not appreciably increase thepumping of blood.

In contrast to certain of the prior art discussed previously, the FFRmeasurement techniques set forth previously utilize continual flow underpower injection in which flow velocity can be controlled, and pressurein the blood vessel V is measured by one or more (e.g., multiple)sensors. Additionally, in the FFR measurement techniques describedpreviously, two pressure readings may be compared and a predetermineddistance between measurement locations is not required. Further, onlyone fluid type, such as contrast media, is required. Moreover, theforegoing FFR measurement techniques include fluid viscosity as aconsideration in the ultimate understanding of the pressure differencesacross the stenosis S.

Referring next or FIG. 37, a fluid delivery system 10 b comprising apower fluid injector 2 b and a control feature or control unit 4 b thatenables the fluid injection system 10 b to be integrated with apressure-sensing and fluid delivery catheter 400 is shown. The fluiddelivery system 10 b further comprises a graphical user interfacedisplay 12 b in a similar manner to that described previously in thisdisclosure. In the fluid delivery system 10 b, the power injector 2 b isintegrated with the pressure catheter 400 to deliver fluid in anoptimized manner based on information obtained by the pressure catheter400. The fluid delivery system 10 b may comprise a syringe-based orpump-based power injector 2 b, appropriate fluid conducting lines, themicroprocessor-based control unit 4 b, the graphical user interfacedisplay 12 b, and the pressure-sensing and fluid delivery catheter 400(hereinafter “catheter 400”). The catheter 400 comprises multiplelumens, one lumen 402 for delivering fluid in the blood vessel V havingthe stenosis S, and a second lumen 404 supporting a guidewire or otherstructure having a single or multiple sensors 406, 408, which aretypically pressure sensors in the present embodiment. Electroniccommunication or connection is between the pressure sensors 406, 408,and the control unit 4 b either in a wired configuration as shown or viawireless connection as will be appreciated by those skilled in the art.The control unit 4 b is further in electronic communication orconnection with the graphical user interface display 12 b and the powerinjector 2 b as illustrated. In the depicted embodiment, the catheter400 is placed in the blood vessel V with one sensor 408 downstream of anobstruction, such as stenosis S, and one sensor 406 is placed upstreamof the stenosis S. Upon user initiation, such as by pressing a button onthe graphical user interface display 12 b, the fluid delivery system 10b delivers fluid, such as contrast media, via the power injector 2 bwithin a set flow rate/range, and the control unit 4 b monitors theupstream pressure via sensor 406 and increases or decreases thepressure/flow based on preprogrammed algorithms to achieve an optimumupstream pressure/flow, enabling a corresponding pressure or flow dropdownstream of the stenosis S. The control unit 4 b further monitors thedownstream pressure via sensor 408 and the upstream pressure via sensor406 and calculates FFR and other desired physiological parameters. Thefluid delivery data stored by the control unit 4 b including pressuredata from the catheter 400 may be combined to provide additionalinformation and analysis including, mean, max, integrals and profiles.The fluid delivery system 10 b also provides real time data and playbackcapabilities in addition to summary data. The fluid delivery system 10 bmay be adapted to conduct fluid injections and collect readingsautomatically from a single user initiation, and provides fluid flow,pressure readings, and final results. Information can be stored inmemory in the control unit 4 b and may be linked to patient procedureinformation including imaging system files as well as being shared withhospital information systems (HIS). In another variation, an aspiration(suction) catheter may be placed downstream of the obstruction, such asstenosis S, and may be controlled by the control unit 4 b to create theoptimized negative pressure to achieve the optimized conditions and tocalculate FFR and other physiological parameters.

Referring to FIGS. 38-39, during a typical FFR interventional case, highblood flows are required to generate a pressure drop across the coronarylesion or stenosis S for cardiologists to measure and determine theextent of occlusion by determining an industry standard FFR ratio(distal pressure/proximal pressure). This high blood flow rate across acoronary lesion will have high linear blood flow velocities. This highblood flow velocity can cause turbulent flow conditions of the blood inthe occluded artery. In fluid mechanics, the Reynolds number (Re) is adimensionless number that gives a measure of the ratio of inertialforces to viscous forces. The Reynolds number is also used tocharacterize different flow regimes, such as laminar or turbulent flow.Laminar flow occurs at low Reynolds numbers, where viscous forces aredominant and is characterized by smooth, constant fluid motion.Turbulent flow occurs at high Reynolds numbers and is dominated byinertial forces, which tend to produce chaotic eddies, vortices, andother flow instabilities. It has experimentally been determined thatturbulent flow rates cause a higher level of mechanical blood damage,also known as “hemolysis”, as known from: Effects of turbulent stressesupon mechanical hemolysis: experimental and computational analysis,Kameneva M V et al. [ASAIO JOURNAL (American Society for ArtificialInternal Organs). 2004 September-October; 50(5):418-23, incorporatedherein by reference]. Reynolds numbers (Re) are calculated per theformula provided below. It is generally accepted that Reynolds numbersabove 2100 are classified as turbulent. The Reynolds number (Re) iscalculated for a flow in a pipe or tube or artery as follows:

${Re} = {\frac{\rho\;{vD}_{H}}{\mu} = {\frac{v\; D_{H}}{v} = \frac{Q\; D_{H}}{v\; A}}}$Where:

D_(H) is the hydraulic diameter of the pipe; its characteristic traveledlength, L, (m).

Q is the volumetric flow rate (m³/s).

A is the pipe cross-sectional area (m²).

v is the mean velocity of the object relative to the fluid (SI units:m/s).

μ is the dynamic viscosity of the fluid (Pa·s or N·s/m² or kg/(m·s)).

ν is the kinematic viscosity (ν=μ/ρ) (m²/s).

ρ is the density of the fluid (kg/m³).

In the present application, Reynolds numbers were calculated forincreasing artery diameter reductions and plotted as shown in FIG. 38.Two curves were generated and plotted from the calculations. The firstcurve (C1) was for adenosine increased arterial blood flow at 5 ml/secin a native coronary artery of 3.9 mm with an occlusion length of 10 mmusing a blood viscosity of 4 cP. The second curve (C2) was for contrastflow at 3.33 ml/sec with an artery the same as above but the contrastviscosity was 11.8 cP. As FIG. 38 shows, when plotted and compared, thecontrast flow curve has lower Reynolds numbers than the adenosine bloodflow curve and, thus, it can be concluded that the level of bloodhemolysis will be less using the contrast based FFR techniques of thepresent disclosure. While the calculations do not consider the reducedflow area due to the presence of a pressure wire, the presence of apressure wire during FFR measurements will only increase Reynoldsnumbers and hemolysis effects using adenosine blood flow.

Additionally, referring to FIG. 39, the contrast flow at 3.33 ml/sec inthe present example produces higher pressure drops than the adenosineblood flow rate at 5 ml/sec due to the viscosity effects of the contrastand will have a more defined FFR value at lower artery diameterreductions. This contrast FFR ratio as shown by first curve (C1-A) canbe transformed to the industry standard FFR value well-known tocardiologists and represented by second curve (C2-A) by simple equationsas follows:FFR Adenosine Value=(((Contrast FFR Value×−0.0492094)+0.491816)+ContrastFFR Value)

While embodiments of an FFR measurement system and method were providedin the foregoing description, those skilled in the art may makemodifications and alterations to these embodiments without departingfrom the scope and spirit of the present disclosure. Accordingly, theforegoing description is intended to be illustrative rather thanrestrictive. The invention described hereinabove is defined by theappended claims and all changes to the invention that fall within themeaning and the range of equivalency of the claims are to be embracedwithin their scope.

The invention claimed is:
 1. A method of determining fractional flowreserve (FFR) in a blood vessel having a stenosis, the methodcomprising: identifying a maximum flow rate through the blood vessel byinjecting a fluid using a fluid delivery system proximal of the stenosisuntil retrograde flow of the fluid is observed; measuring with an atleast one pressure sensor a first pressure in the blood vessel proximalof the stenosis and a second pressure in the blood vessel distal of thestenosis during the injecting of the fluid at the maximum flow rate;measuring a first pressure drop across the stenosis based on the firstpressure and the second pressure using the fluid delivery system; andcalculating a first FFR from the first pressure drop using the fluiddelivery system.
 2. The method of claim 1, wherein the measuring of thefirst pressure comprises placing the at least one pressure sensorproximal of the stenosis, and wherein the measuring of the secondpressure comprises placing the at least one pressure sensor distal ofthe stenosis.
 3. The method of claim 1, wherein the injecting of thefluid using the fluid delivery system is reduced or discontinued after apreset period of time.
 4. The method of claim 1, wherein the measuringof the first pressure drop across the stenosis comprises calculating aratio of the second pressure to the first pressure.
 5. The method ofclaim 1, wherein the first pressure and the second pressure are measuredsimultaneously.
 6. The method of claim 1, further comprising validatingthe first FFR using the fluid delivery system.
 7. The method of claim 6,wherein the validating of the first FFR comprises: reinjecting the fluidusing the fluid delivery system at the maximum flow rate; measuring withthe at least one pressure sensor a third pressure in the blood vesseldistal of the stenosis and a fourth pressure in the blood vesselproximal of the stenosis during the reinjecting of the fluid; measuringa second pressure drop across the stenosis based on the third pressureand the fourth pressure using the fluid delivery system; and calculatinga second FFR from the second pressure drop using the fluid deliverysystem.
 8. The method of claim 7, wherein the measuring of the thirdpressure comprises placing the at least one pressure sensor distal ofthe stenosis, and wherein the measuring of the fourth pressure comprisesplacing the at least one pressure sensor proximal of the stenosis. 9.The method of claim 7, wherein the measuring of the second pressure dropacross the stenosis comprises calculating a ratio of the third pressureto the fourth pressure.
 10. The method of claim 7, further comprisingfiltering with the fluid delivery system the third pressure and thefourth pressure to exclude mean arterial pressure.
 11. The method ofclaim 1, wherein a flow rate of the fluid injected into the blood vesselis controlled by the fluid delivery system.
 12. The method of claim 1,wherein a pressure of the fluid injected into the blood vessel iscontrolled by the fluid delivery system.
 13. The method of claim 1,wherein the injected fluid comprises a contrast medium.
 14. A method ofdetermining fractional flow reserve (FFR) in a blood vessel having astenosis, the method comprising: inserting a multi-lumen catheter intothe blood vessel; identifying a maximum flow rate through the bloodvessel by injecting a fluid using a fluid delivery system proximal ofthe stenosis until a retrograde flow of the fluid is observed; measuringa first pressure in the blood vessel proximal of the stenosis and asecond pressure in the blood vessel distal of the stenosis duringinjecting of the fluid at the maximum flow rate; measuring a firstpressure drop across the stenosis based on the first pressure and thesecond pressure using the fluid delivery system; reducing ordiscontinuing the injecting of the fluid when the retrograde flow ispresent in the blood vessel; and calculating a first FFR from the firstpressure drop using the fluid delivery system.
 15. The method of claim14, wherein the injecting of the fluid using the fluid delivery systemis reduced or discontinued after a preset period of time.
 16. The methodof claim 14, wherein the measuring of the first pressure drop across thestenosis comprises calculating a ratio of the second pressure to thefirst pressure.
 17. The method of claim 14, wherein the first pressureand the second pressure are measured simultaneously using an at leastone pressure sensor and a hemodynamic monitoring port on the multi-lumencatheter.
 18. The method of claim 14, further comprising validating thefirst FFR using the fluid delivery system, wherein the validating of thefirst FFR comprises: reinjecting the fluid using the fluid deliverysystem at the maximum flow rate; measuring a third pressure in the bloodvessel distal of the stenosis and a fourth pressure in the blood vesselproximal of the stenosis during the reinjecting of the fluid; measuringa second pressure drop across the stenosis based on the third pressureand the fourth pressure using the fluid delivery system; and calculatinga second FFR from the second pressure drop using the fluid deliverysystem.
 19. The method of claim 18, wherein the measuring of the secondpressure drop across the stenosis comprises calculating a ratio of thethird pressure to the fourth pressure.
 20. The method of claim 14,wherein the multi-lumen catheter comprises at least a fluid injectinglumen and a hemodynamic monitoring lumen.